OVERALL OBJECTIVES: (1) Test known organisms and those isolated from soil by the enrichment culture technique for production of enzymes which possess certain predetermined characteristics and are capable of degrading the following amino acids in vivo: glutamine, arginine, citrulline, histidine and serine. (2) Develop optimal methods of purifying in high yield each enzyme to a homogeneous state. (3) Investigate the kinetic and physical characteristics of each enzyme with emphasis on those properties which are most related to the enzyme's ability to function effectively in vivo. (4) Study the effects of prolonged enzyme treatment on plasma and tissue stores of amino acids in animals. (5) Evaluate the antineoplastic efficacy of single- and multi-enzyme therapy, as well as enzyme therapy combined with the appropriate amino acid analogs. (6) Determine the toxicity of new enzymes in animals. (7) If needed, chemically or physically alter the enzymes to extend their biological half-life, reduce their immunogenicity and improve their distribution outside the vascular space so as to increase their effectiveness on solid tumors.